The regulation of growth and reproduction has been investigated using murine and non-human primate models. It has been established that locally produced insulin-like growth factor I (IGF-I) regulates postnatal brain growth by augmenting neuronal glucose utilization in an autocrine/paracrine fashion. It has also been demonstrated that contrary to the common assumption, brain IGF-I does not play a major role in brain myelination. In the study of reproduction, it has been shown that local IGF-I expression regulates ovarian gonadotropin sensitivity and entrains follicular development to regulation by the pituitary. It has also been demonstrated that local IGF-I expression is not necessary for estrogen-induced DNA synthesis by uterine cells (i.e., entry into the cell cycle and progression through G1 into S-phase), but is essential for completion of mitosis and hence estrogen-induced uterine growth. This finding appears to have major significance in showing for the first time that extracellular signaling may regulate late phases of the cell cycle. Finally, treatment of aging female rhesus monkeys (a non-human primate model for menopause) with growth hormone (GH) or IGF-I has been found to stimulate marked mammary epithelial, hyperplasia, suggesting that GH or IGF-I treatment of elderly women may increase their risk for breast cancer.